Exportin-5-mediated nuclear export of eukaryotic elongation factor 1A and tRNA

Calado, Ângelo; Treichel, Nathalie; Müller, Eva‐Christina; Otto, Albrecht; Kutay, Ulrike

doi:10.1093/emboj/cdf620

Cited by 184 publications

(198 citation statements)

References 43 publications

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“…It has also been shown that interaction between in vitro translated ILF3 and exportin-5 was affected upon RNase treatment suggesting that the complex between these proteins was RNA-mediated (8).…”

Section: Ilf3mentioning

confidence: 99%

“…eEF1A is a GTP-binding protein that interacts with aminoacetylated tRNA and catalyzes their binding to the ribosome. Complex formation between eEF1A and exportin-5 was shown to be strictly dependent on aminoacetylated tRNAs that bridge both proteins (8,9). Indeed, tRNAs present a highly degenerated minihelix motif able to directly interact with exportin-5, although with a lower affinity than an optimal minihelix structure.…”

mentioning

confidence: 99%

“…Indeed, tRNAs present a highly degenerated minihelix motif able to directly interact with exportin-5, although with a lower affinity than an optimal minihelix structure. Consistently, tRNAs do not represent a preferential cargo for exportin-5 but can use this alternative transport receptor when their own export pathway mediated by exportin-t is deficient (6,8). ILF3 is a nuclear protein that presenting two double-stranded RNA binding domains (dsRBDs), as well as an RGG domain.…”

mentioning

confidence: 99%

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Minihelix-containing RNAs Mediate Exportin-5-dependent Nuclear Export of the Double-stranded RNA-binding Protein ILF3

Gwizdek

Ossareh-Nazari

Brownawell

et al. 2004

Journal of Biological Chemistry

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The karyopherin-related nuclear transport factor exportin-5 preferentially recognizes and transports RNAs containing minihelix motif, a structural cis-acting export element that comprises a double-stranded stem (>14 nucleotides) with a base-paired 5 end and a 3-8-nucleotide protruding 3 end. This structural motif is present in various small cellular and viral polymerase III transcripts such as the adenovirus VA1 RNA (VA1). Here we show that the double-stranded RNA-binding protein, ILF3 (interleukin enhancer binding factor 3) preferentially binds minihelix motif. Gel retardation assays and glutathione S-transferase pull-down experiments revealed that ILF3, exportin-5, RanGTP, and VA1 RNA assembled in a quaternary complex in which the RNA moiety bridges the interaction between ILF3 and exportin-5. Formation of this complex is facilitated by the ability of both exportin-5 and ILF3 to mutually increase their apparent affinity for VA1 RNA. Using microinjection in the nucleus of HeLa cells and transfection experiments, we show here that formation of the cooperative RanGTP-dependent RNA/ILF3/exportin-5 complex promotes the co-transport of VA1 and ILF3 from the nucleus to the cytoplasm. Exportin-5 thus appears as the first example of a nuclear export receptor that mediates RNA export but also promotes transport of proteinaceous cargo through appropriate and specific RNA adaptors.Transfer of macromolecules through nuclear pore complexes depends on both structural components of nuclear pore complexes and soluble factors that ensure nuclear transport of a wide diversity of cellular proteins and RNAs. Selectivity of transport is mediated by the recognition of specific signals within the cargoes by specific transport receptors through a direct or adaptor-mediated interaction. Transport receptors interact with nucleoporins thereby mediating docking to and translocation through the nuclear pore complexes. Most of the transport receptors belong to the karyopherin ␤ family (also known as importin ␤ family) and use the GTPase Ran to control cargo association. The asymmetric distribution of the Ran regulatory proteins provides a steep gradient of RanGDP (cytoplasmic)/RanGTP (nuclear) across the nuclear envelope that ensures the directionality of nuclear transport (1, 2). Indeed, nuclear import receptors (importins) bind their cargoes in the cytoplasm in the absence of RanGTP and unload them upon binding to RanGTP in the nucleus. In contrast, export receptors (exportins) require RanGTP to interact with their cargoes in the nucleus, and those export complexes are destabilized by dissociation of RanGTP and GTP hydrolysis in the cytoplasm (3, 4).Study of nuclear export pathways of diverse viral RNAs has greatly contributed to the identification of cellular factors implicated in nuclear transport processes. In particular, we recently reported nuclear export mechanisms of the adenovirus VA1 RNA (5, 6). This RNA is abundantly transcribed by RNA polymerase III and efficiently exported to the cytoplasm in the late phase of the viral infect...

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Section: Ilf3mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Minihelix-containing RNAs Mediate Exportin-5-dependent Nuclear Export of the Double-stranded RNA-binding Protein ILF3

Gwizdek

Ossareh-Nazari

Brownawell

et al. 2004

Journal of Biological Chemistry

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“…52 They interact with the importin-and exportin-mediated transport of proteins in and out of the nucleus. 53 Three clones of the PTX induced genes exhibit similarity to the same asparaginyl b-hydroxylase mRNA transcribed from ASPH (clone 1.20, 1.27 and 1.28). Conservation of this gene up till human species suggests that the ASPH holds important functional roles.…”

Section: Insert-comparison With Genomic Databasesmentioning

confidence: 98%

Induced and repressed genes after irradiation sensitizing by pentoxyphylline

Waldeck

Strunz

Müller

et al. 2006

Intl Journal of Cancer

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Aim in cancer therapy is to increase the therapeutic ratio eliminating the disease while minimizing toxicity to normal tissues. Radiation therapy is a main component in targeting cancer. Radiosensitizing agents like pentoxyphylline (PTX) have been evaluated to improve radiotherapy. Commonly, cells respond to radiation by the activation of specific early and late response genes as well as by inhibition of genes, which are expressed under normal conditions. A display of the genetic distinctions at the level of transcription is given here to characterize the molecular events underlying the radiosensitizing mechanisms. The method of suppression subtractive hybridization allows the visualization of both induced and repressed genes in irradiated cells compared with cells sensitized immediately after irradiation. The genes were isolated by cDNA-cloning, differential analysis and sequence similarity search. Genes involved in protein synthesis, metabolism, proteolysis and transcriptional regulation were detected. It is important that genes like KIAA280, which were only known as unidentified EST sequences before without function, but inaccessible by array technology were recovered as functional genes. Database searches for PTX-induced genes detected a human mRNA completely unknown. In case of suppressed genes, we detected several mRNAs; one thereof shows homology to a hypothetical protein possibly involved in signal transduction. A further mRNA encodes the protein BM036 supposed to associate with the E2F transcription factor. A hypothetical protein H41 was detected, which may repress the Her-2/neu receptor influencing breast cancer, gliomas and prostate tumors. Radiation combined with PTX may lead to a better prognosis by down regulation of the Her-2/neu, which will be proven by clinical studies in the near future. The connection between cancerogenesis and cyclins has been demonstrated with the aberrant expression of members of the family of cyclins and the mechanisms of the cell cycle G1 arrest and apoptosis were well documented. [3][4][5][6][7] The mechanisms of G2 arrest in contrast have been described to a lesser extent, although this event could be of relevance to the cellular survival after photonirradiation. 8,9 Beyond doubt, the G2-phase arrest is generally activated in response to DNA damage independent of the p53 status. 8 It acts as an universal feedback for maintaining the genomic integrity and for survival after irradiation by repairing DNA breaks prior to mitosis. 10 Much of the underlying knowledge on the G2/M phase was obtained by studying genes involved in the regulation of DNA damage response because DNA-damaging processes, like g-radiation, respond by arresting at cell cycle checkpoints. 11 This ''G2 delay'' after photon-irradiation involves molecular mechanisms like reduced cyclin B levels and inhibition of the Cdk1 activity. 8 Formation and activation of the maturation promoting factor (MPF) are pivotal for the G2/M checkpoint regulation. The transition from G2 into the mitosis occurs by the activatio...

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“…The mamallian (Exp5) and Drosophila (dmExp5) orthologs of Msn5 have also been implicated in tRNA transport (Bohnsack et al 2002;Calado et al 2002;Shibata et al 2006). Defects in tRNA re-export can be monitored by genetic and biochemical means.…”

Section: Introductionmentioning

confidence: 99%

P-body components, Dhh1 and Pat1, are involved in tRNA nuclear-cytoplasmic dynamics

Hurto¹,

Hopper²

2011

RNA

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The nuclear-cytoplasmic distribution of tRNA depends on the balance between tRNA nuclear export/re-export and retrograde tRNA nuclear import in Saccharomyces cerevisiae. The distribution of tRNA is sensitive to nutrient availability as cells deprived of various nutrients exhibit tRNA nuclear accumulation. Starvation induces numerous events that result in translational repression and P-body formation. This study investigated the possible coordination of these responses with tRNA nuclearcytoplasmic distribution. Dhh1 and Pat1 function in parallel to promote translation repression and P-body formation in response to starvation. Loss of both, Dhh1 and Pat1, results in a failure to repress translation and to induce P-body formation in response to glucose starvation. This study reports that nutrient deprived dhh1 pat1 cells also fail to accumulate tRNA within nuclei. Conversely, inhibition of translation initiation and induction of P-body formation by overproduction of Dhh1 or Pat1 cause tRNA nuclear accumulation in nutrient-replete conditions. Also, loss of the mRNA decapping activator, Lsm1, causes tRNA nuclear accumulation. However, the coordination between P-body formation, translation repression, and tRNA distribution is limited to the early part of the P-body formation/translation repression pathway as loss of mRNA decapping or 59 to 39 degradation does not influence tRNA nuclear-cytoplasmic dynamics. The data provide the first link between P-body formation/translation initiation and tRNA nuclear-cytoplasmic dynamics. The current model is that Dhh1 and Pat1 function in parallel to promote starvation-induced tRNA nuclear accumulation.

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Exportin-5-mediated nuclear export of eukaryotic elongation factor 1A and tRNA

Cited by 184 publications

References 43 publications

Minihelix-containing RNAs Mediate Exportin-5-dependent Nuclear Export of the Double-stranded RNA-binding Protein ILF3

Minihelix-containing RNAs Mediate Exportin-5-dependent Nuclear Export of the Double-stranded RNA-binding Protein ILF3

Induced and repressed genes after irradiation sensitizing by pentoxyphylline

P-body components, Dhh1 and Pat1, are involved in tRNA nuclear-cytoplasmic dynamics

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